Survival in Patients With Cervical Cancer Treated With Radiotherapy According to SOX1 and PAX1 Methylation Profiles

Abstract

PURPOSE To evaluate cancer-specific survival (CSS) in patients with cervical cancer treated with radiotherapy and its association with SOX1 and PAX1 DNA methylation status. METHODS This prospective observational study included 46 patients with cervical cancer treated with primary radiotherapy between 2022 and 2025 in Campinas, Brazil. Tumor samples were analyzed for SOX1 and PAX1 methylation using quantitative methylation-specific PCR. Methylation cutoffs were defined based on previous ROC analyses. CSS was estimated using Kaplan–Meier curves and compared using the log-rank test. Hazard ratios (HR) and 95% CIs were calculated using Cox proportional hazards models, with adjustment for age, BMI, and histological type. RESULTS PAX1 methylation status was associated with survival outcomes. Patients with PAX1 hypomethylation had a higher risk of death compared with those with hypermethylation (HR 4.55; 95% CI 1.30 to 15.87), which remained significant after adjustment (HR 4.90; 95% CI 1.29 to 18.52). Median CSS was shorter in the hypomethylated group (13.0 months) than in the hypermethylated group (16.3 months) ( P = .010). Differences in survival became more evident over time, with 12-month CSS rates of 56.0% versus 89.4%, and 24-month rates of 28.0% versus 83.0% for hypomethylated and hypermethylated groups, respectively. In FIGO stage III/IV disease, hypomethylation was also associated with lower 12-month survival (46.4% v 82.5%), although this did not reach statistical significance (p=0.056). SOX1 methylation was not associated with survival ( P = .561). No significant associations were observed for age, BMI, histological type, or grade. CONCLUSION PAX1 hypomethylation was associated with worse prognosis in cervical cancer patients treated with radiotherapy, with higher risk of death and shorter survival, particularly in advanced-stage disease. To our knowledge, this is the first study in a Western population evaluating the methylation status of PAX1 and SOX1 in relation to cervical cancer survival. Further studies in larger cohorts are needed to confirm these findings and better understand the role of SOX1 as a prognostic marker.

The authors' abstract, as published at the source. JCO Global Oncology, 2026 · DOI ↗